Presenilin-1 exists in both pre- and post-golgi compartments and recycles via COPI-coated membranes

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Presenilin-1 exists in both pre- and post-golgi compartments and recycles via COPI-coated membranes

Réchards, M.; Xia, W.; Oorschot, V.; Selkoe, D.J.; Klumperman, J.

(2003) Traffic, volume 4, issue 8, pp. 553 - 565

(Article)

Abstract

Presenilin-1 is involved in intramembrane proteolysis of various proteins, but its intracellular site of action has remained elusive. Here, we determined by quantitative
immunogold-electron microscopy that presenilin-1 in Chinese hamster ovary cells is present in pre-Golgi compartments as well as at the plasma membrane and endosomes. Notably, a high percentage of ... read more presenilin-1
resides in COPI-coated membranes between the endoplasmic reticulum and the Golgi complex, indicating significant recycling to the endoplasmic reticulum. By contrast, the inactive aspartate mutant presenilin-1 D257A
is relatively excluded from COPI-coated membranes, concomitant with increased post-Golgi levels. These data provide critical evidence for the scenario that the complex containing presenilin-1 can serve as g-secretase at the plasma membrane or endosomes and suggest a role for COPI-mediated retrograde transport in regulating
post-Golgi levels of presenilin-1. show less

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